PD-1-Enhanced Treg Cell Senescence in Advanced Maternal Age

Senescence occurs earlier in the immune system than in solid organs as age increases. Regulatory T (Treg) cells are among the first cells to exhibit signs of aging. However, whether advanced-age pregnancy involves Treg cell aging remains unclear. This study demonstrated that the aging of women is accompanied by aging Treg cells and that PD-1 regulates Treg cell aging. The transfer of young Treg cells can improve the pregnancy outcomes of reproductive-aged mice by reducing the level of IFN-γ, a proinflammatory cytokine secreted by Treg cells in aged mice. Transferring α-PD-1 mAb-treated aged Treg cells increases the level of IL-10, an anti-inflammatory cytokine secreted by Treg cells in reproductive-aged mice. Collectively, these findings suggest a potential therapeutic strategy for preventing adverse pregnancy outcomes in older women.